Differential expression of TNFR1 (CD120a) and TNFR2 (CD120b) on subpopulations of human monocytes

Abstract

BackgroundThree subpopulations of monocytes can be distinguished in human blood: classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++). CD16 expressing monocytes are expanded in patients with sarcoidosis and in various other inflammatory diseases. In sarcoidosis, it is unclear whether either intermediate, nonclassical or both CD16 expressing monocytes are responsible for this increase. Data relating to the monocyte subpopulations is receiving increasing attention, but the expression of TNF receptors on these subpopulations has not been studied thus far. The aim of this study was to determine frequencies of monocyte subpopulations and their expression of TNFR1 and TNFR2 in both sarcoidosis patients and healthy controls.MethodsPeripheral blood cells of sarcoidosis patients and healthy controls were stained for the markers HLA-DR, CD14, CD16, CD120a and CD120b. Cells were measured on a FACSCalibur and analyzed with FlowJo. We used Student’s t-test and a parametric One-way ANOVA for statistical analysis.ResultsSarcoidosis patients had a significant higher frequency of intermediate monocytes than healthy controls. Significant differences in TNF receptor expression were found between the monocyte subpopulations, both in sarcoidosis patients as well as in healthy controls: intermediates expressed more TNFR1 than classicals and nonclassicals and nonclassicals expressed more TNFR2 than intermediates, whereas intermediates showed higher expression than classicals.ConclusionsIn both sarcoidosis patients and healthy controls intermediate monocytes show the highest expression level of TNFR1 among monocyte subpopulations and nonclassical monocytes show the highest expression level of TNFR2. These findings, as wells as the higher frequency of intermediate monocytes in sarcoidosis patients, provide evidence for the existence of two functionally-distinct CD16 expressing monocyte subpopulations.

NLRP6 function in inflammatory monocytes reduces susceptibility to chemically induced intestinal injury

“…24, 26-28 Although there has been conflicting data that demonstrate a pathogenic role for TNFR2 in DSS-induced colitis, 29 inflammatory monocytes are more likely to express TNFR1, while TNFR2 upregulation in colonic epithelial cells is observed in patients with inflammatory bowel disease. 30, 31 Altogether, these studies are consistent with our data since Nlrp6 −/− mice that receive rTNFα early during DSS treatment exhibit reduced intestinal inflammation and bacterial translocation.…”

IL-12–producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion

“…A possibility is that CD16 was lost due to cellular activation via TLRs, as previously shown (29). We therefore defined the IL-12-producing subpopulation as HLA-DR + , CD38 lo , and CD120b + , which is consistent with the phenotype of inflammatory monocytes (29,30). Notably, the production of IL-12 by CD16 +…”

Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis

“…We also demonstrated that in patients with sarcoidosis the intermediate CD16 + CD14 ++ blood monocyte population was expanded. Since this monocyte subset has been shown to express the highest levels of the TNF receptor TNFR131, monocytes in sarcoidosis may be more responsive to TNF.…”